TIVA & TCI Sedation

1. TIVA & TCI Sedation Dr James F Peerless November 2012

2. Objectives • TIVA & TCI • What, why, when, where and how • Models, Monitoring & Limitations • Context-Sensitive Half-Time • Suitability of drugs for TCI

3. TCI • “Target-Controlled Infusion” • An infusion system whereby the target concentration of a particular agent is selected.

4. TIVA • “Total IntraVenousAnaesthesia” • Anaesthesia provided solely by IV route • Generally as an infusion which is titrated at a specific rate to achieve a specific concentration • Cp – plasma concentration • Ce – effect site concentration

5. Indications/Benefits • When: • Inhalational agents unavailable • Administering inhalational agents is difficult • Inhalational agents are contraindicated • Patient has severe PONV • Also: • Reduces staff exposure to inhalational agents • Reduces pollution • NOT: • Unmonitored sedation at home

6. Pharmacokinetics

7. Pharmacokinetics

8. Why do we use models? • At present in clinical use there is no method of measuring drug concentrations real time analogous to the end tidal volatile agent concentration • Models only – no actual plasma measurements • Most models describe healthy volunteers and there is poor correlation in unwell patients • The trend of increasing obesity does alter pharmacokinetics and accuracy of the pumps

9. Models • Propofol • Marsh model • 3-compartment model optimised by weight, gender & age • Schnider model • Diprivan 2% prefilled syringes • Remifentanil • Minto model • Made up to 50 mcg mL-1 (2 mg in 40 mL 0.9% N. Saline)

10. Induction of Anaesthesia • Good IV access – visible at all times!! • Dedicated line where possible • Ensure a dripping drip • Anti-reflux valves • Minimise dead-space

11. Induction of Anaesthesia • Select a target concentration • Press ‘go’ • Ensure adequate O2 • Change settings/increase the target concentration in slow, small stages

12. Numbers! • Propofol TCI • Sedation: 1 – 2 mcg mL-1 • Anaesthesia EC50: 6 – 7 mcg mL-1 • Remifentanil • 0.05 – 0.5 mcg kg-1 min-1 • TCI: 4 – 8 ng mL-1 • Bear in mind individual variations in pharmacokinetics and drug interactions

13. Limitations • Inability to monitor actual drug concentration • Slow recovery/wake-up after long operations due to distribution across compartments • Increased cost compared with volatile agents • Interruption to TCI delivery may go unnoticed longer than with volatiles • [fighting with other theatres for use of PK pumps]

14. Context-Sensitive Half-Time • The CSHT is: “The time taken for the drug concentration to reduce by half once an infusion designed to maintain a constant plasma concentration is stopped.” • CSHT for a specific drug will vary depending on the length of the infusion

15. CSHT • During an infusion, drugs will accumulate and equilibrate within all the tissues/compartments. • The longer the duration of the infusion, the higher the degree of accumulation, which will maintain plasma levels once the infusion is stopped. • As a result, some drugs are better suited to infusions than others

16. Upon Stopping the Infusion

17. Ideal drugs • Small VD • Rapid metabolism (no active metabolites) • High Cl • Short CSHT • Propofol, alfentanil, remifentanil

18. Remifentanil – wow! • Rapidly metabolised • Non-specific plasma and tissue esterases • Short t1/2elim • 1.3 minutes • High Cl • 2.5 L kg-1 hr-1 • Small VD • 0.35 L kg-1 = context-“insensitive” half-time

19. Context-Sensitive Half-Time Fentanyl Thiopental CSHT (min) Alfentanil Propofol Remifentanil Duration of Infusion (hr)

20. Summary • Target concentrations are calculated, not measured • TCI pumps maintain three superimposed infusions, one at a constant rate to replace drug elimination and two exponentially decreasing infusions to match drug removed from central compartment to other peripheral compartments of distribution


21. Questions?